Related Experiment Video
Updated: Feb 21, 2026
Measuring Progressive Neurological Disability in a Mouse Model of Multiple Sclerosis
Published on: November 14, 2016
Evaluating Treatment Efficacy in a Mouse Model of Enterovirus D68-Associated Paralytic Myelitis
Alison M Hixon1,2, Penny Clarke3, Kenneth L Tyler3,4,5
1Medical Scientist Training Program.
Background:
Enterovirus D68 (EV-D68)-associated acute flaccid myelitis (AFM) is a devastating neurological disease for which there are no treatments of proven efficacy. The unpredictable temporal and geographic distribution of cases and the rarity of the disease make it unlikely that data from randomized controlled trials will be available to guide therapeutic decisions. We evaluated the following 3 widely used empirical therapies for the ability to reduce the severity of paralysis in a mouse model of EV-D68 infection: (1) human intravenous immunoglobulin (hIVIG), (2) fluoxetine, and (3) dexamethasone.
Methods:
Neonatal mice were injected intramuscularly with a human 2014 EV-D68 isolate that reliably induces paralysis in mice due to infection and loss of spinal cord motor neurons. Mice receiving treatments were evaluated for motor impairment, mortality, and spinal cord viral load.
Results:
hIVIG, which contained neutralizing antibodies to EV-D68, reduced paralysis in infected mice and decreased spinal cord viral loads. Fluoxetine had no effect on motor impairment or viral loads. Dexamethasone treatment worsened motor impairment, increased mortality, and increased viral loads.
Conclusion:
Results in this model of EV-D68-associated AFM provide a rational basis for selecting empirical therapy in humans and establish this model as a useful system for evaluating other potential therapies.
Insights
Human intravenous immunoglobulin (hIVIG) reduced paralysis in a mouse model of Enterovirus D68 (EV-D68) infection. Dexamethasone worsened outcomes, while fluoxetine had no effect, guiding potential treatments for acute flaccid myelitis (AFM).
Area of Science:
- Neurology
- Virology
- Immunology
Background:
- Enterovirus D68 (EV-D68) causes acute flaccid myelitis (AFM), a severe neurological condition with no proven treatments.
- The rarity and unpredictable nature of AFM limit the feasibility of randomized controlled trials for therapy selection.
Purpose of the Study:
- To evaluate the efficacy of three empirical therapies—human intravenous immunoglobulin (hIVIG), fluoxetine, and dexamethasone—in a mouse model of EV-D68 infection.
- To determine the impact of these therapies on paralysis severity, mortality, and viral load.
Main Methods:
- Neonatal mice were infected with a 2014 EV-D68 isolate to induce paralysis and motor neuron loss.
- Mice received either hIVIG, fluoxetine, or dexamethasone and were assessed for motor impairment, mortality, and spinal cord viral load.
Main Results:
- hIVIG, containing neutralizing antibodies, significantly reduced paralysis and spinal cord viral loads in infected mice.
- Fluoxetine treatment showed no significant effect on motor impairment or viral load.
- Dexamethasone administration exacerbated motor impairment, increased mortality, and elevated viral loads.
Conclusions:
- The study provides evidence supporting hIVIG as a potential therapeutic option for EV-D68-associated AFM.
- Dexamethasone appears detrimental in this model and should be used cautiously.
- This mouse model is valuable for evaluating novel therapies against EV-D68 and AFM.
